Through the activities in this Technology Core, we will provide comprehensive high-throughput genome sequencing and analysis to the investigators participating in this U19 proposal to advance research in all four projects that are focused on understanding host, pathogen, and microbiome interactions as determinants of infectious disease outcome. We will provide standard high throughput genome, transcriptome, metagenome, metatranscriptome, and single cell sequencing as well as other standard sequencing methods required by our Viral, Bacterial, Fungal, and Parasite research projects and any future collaborative pilot projects. This includes sequencing on every major sequencing platform including Illumina, Pacific Biosciences, and Oxford Nanopore. We will also provide custom sequencing approaches for the study of infectious disease, when necessary, building on our immense experience on sequence and analysis of polymicrobial samples. We will use the latest sequencing and analysis tools to improve genome annotation, providing an important resource to the infectious disease community. We will focus our research and development activities on developing a robust single cell transcriptomics for the analysis of host-pathogen samples, including single cell transcriptomics on prokaryotic pathogens lacking polyadenylated transcripts. We will encourage and support the implementation and analysis of genome editing approaches that are described within the projects. Lastly, we will integrate our Technology and Data Cores to seamlessly transition sequencing data and novel analysis tools generated in the Technology Core to the Data Core.